Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902-6000, USA.
Pharmacol Biochem Behav. 2012 Dec;103(2):284-94. doi: 10.1016/j.pbb.2012.08.004. Epub 2012 Aug 17.
Exposure to an immunogen results in a constellation of behavioral changes collectively referred to as "sickness behaviors," with alterations in cytokine expression previously shown to contribute to this sickness response. Since behaviors observed during ethanol withdrawal are strikingly similar to sickness behaviors, we hypothesized that behavioral manifestations of ethanol withdrawal might be an expression of sickness behaviors induced by ethanol-related changes in peripheral and/or central cytokine expression. Accordingly, behaviors exhibited during a modified social investigation test were first characterized in male rats following an acute injection of lipopolysaccharide (LPS; 100μg/kg). Subsequently, behavioral changes after either a high (4-g/kg; Experiment 2) or low dose (0.5g/kg; Experiment 3) of ethanol were also examined in the same social investigation test, as well as in the forced-swim test (FST; Experiment 4). Results from these experiments demonstrated similar reductions in both exploration and social investigatory behavior during acute illness and ethanol withdrawal, while a seemingly paradoxical decrease in immobility was observed in the FST during acute ethanol withdrawal. In follow-up studies, neither indomethacin (Experiment 5) nor interleukin-1 receptor antagonist (Experiment 6) pre-exposure reversed the ethanol withdrawal-induced behavioral changes observed in this social investigation test. Taken together, these studies demonstrate that the behavioral sequelae of acute illness and ethanol withdrawal are similar in nature, while antagonist studies suggest that these behavioral alterations are not reversed by blockade of IL-1 receptors or inhibition of prostaglandin synthesis. Though a direct mechanistic link between cytokines and the expression of acute ethanol withdrawal-related behaviors has yet to be found, future studies examining the involvement of brain cytokines as potential mediators of ethanol effects are greatly needed.
暴露于免疫原会导致一系列行为改变，统称为“疾病行为”，先前的研究表明细胞因子表达的改变有助于这种疾病反应。由于乙醇戒断期间观察到的行为与疾病行为非常相似，我们假设乙醇戒断的行为表现可能是由乙醇相关的外周和/或中枢细胞因子表达变化引起的疾病行为的表达。因此，在雄性大鼠中，首先在急性注射脂多糖（LPS；100μg/kg）后，对改良社会调查测试中表现出的行为进行了特征描述。随后，在相同的社会调查测试中，还检查了高（4g/kg；实验 2）或低剂量（0.5g/kg；实验 3）乙醇后行为的变化，以及在强迫游泳测试（FST；实验 4）中。这些实验的结果表明，在急性疾病和乙醇戒断期间，探索和社交探究行为都相似地减少，而在急性乙醇戒断期间，FST 中观察到的不动性似乎呈下降趋势。在后续研究中，既没有吲哚美辛（实验 5）也没有白细胞介素-1 受体拮抗剂（实验 6）预先暴露可逆转在这种社会调查测试中观察到的乙醇戒断引起的行为变化。总的来说，这些研究表明急性疾病和乙醇戒断的行为后果在性质上是相似的，而拮抗剂研究表明，这些行为改变不能通过阻断 IL-1 受体或抑制前列腺素合成来逆转。尽管尚未找到细胞因子与急性乙醇戒断相关行为表达之间的直接机制联系，但需要进行更多研究来检验大脑细胞因子作为潜在的乙醇作用介导物的参与。
